The fusion of myeloma cells and B lymphocytes to form hybridomas which produce monoclonal antibodies has been a major advance in recent biomedical research. See Nature, 256, 495-497 (1975); Nature 266, 550-552 (1977) and Eur. J. Pharm. 6, 511-519 (1976). However, the effectiveness of the process has been hampered by a number of disadvantages, particularly its lack of specificity in terms of the cells which are fused. Usually Sendai virus or polyethylene glycol have been used to induce cell fusion but these materials are normally of poor efficiency, the frequency of successful fusion being usually less than 10.sup.-5. Furthermore, the cell fusion obtained by these methods is nonspecific so that all cells are fused at random whether or not the lymphocytes involved are the type that make antibodies to an appropriate antigen. Typically only a small fraction of myeloma-lymphocyte hybridomas produce antibodies of interest. Extensive immunization with large amounts of antigen has been attempted in efforts to improve the yield of monoclonal antibodies. However, this is not a feasible technique when only a small amount of the antigen is available. Additionally, the high frequency of random fusion requires a stringent, extensive and often laborious screening process to separate out and recover the desired monoclonal antibodies.
High voltage electrical fields have also been employed for cell fusion. See, for example, Sixth Int. Biophys Cong. Kyoto Abstr. IV-19(H), p. 140 (1978); Naturwissenschaften 67, 414-145 (1980); Current Genetics 4, 165-166 (1981); and Science 216, 537-538 (1982). When used in conjunction with dielectrophoresis to secure cell alignment, quantitative cell fusion can be obtained. See "Dielectrophoresis", Cambridge University Press, Cambridge (1978); and Biochim. Biophys. Acta 694, 227-277 (1982). Usually a limited number of cells are fused at a time under direct microscopic examination. Direct visualization can distinguish cells with different morphology, but one cannot identify those B-cells destined to secrete the relevant antibodies.
It is also known that B-cells (lymphocytes) express on their surface antigen "receptor" immunoglobulins of the same antigenic specificity as the antibodies secreted therefrom. Antigens are selectively bound to such surface receptors and when so bound stimulate proliferation and differentiation of B-cells into plasma cells, which then secrete antibodies.